Nanoscale imaging reveals laterally expanding antimicrobial pores in lipid bilayers

Antimicrobial peptides are postulated to disrupt microbial phospholipid membranes. The prevailing molecular model is based on the formation of stable or transient pores although the direct observation of the fundamental processes is lacking. By combining rational peptide design with topographical (a...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 110; no. 22; pp. 8918 - 8923
Main Authors Rakowska, Paulina D., Jiang, Haibo, Ray, Santanu, Pyne, Alice, Lamarre, Baptiste, Carr, Matthew, Judge, Peter J., Ravi, Jascindra, Gerling, Ulla I. M., Koksch, Beate, Martyna, Glenn J., Hoogenboom, Bart W., Watts, Anthony, Crain, Jason, Grovenor, Chris R. M., Ryadnov, Maxim G.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 28.05.2013
National Acad Sciences
Subjects
Amino Acid Sequence
Antimicrobial agents
Antimicrobial Cationic Peptides - chemistry
Antimicrobial Cationic Peptides - genetics
Antimicrobial Cationic Peptides - metabolism
antimicrobial peptides
Antimicrobials
Atomic force microscopy
Biochemistry
Biological Sciences
Chromatography, High Pressure Liquid
Circular Dichroism
image analysis
Imaging
Line spectra
Lipid bilayers
Lipid Bilayers - chemistry
Lipids
Magnetic Resonance Spectroscopy
Mass Spectrometry
Membranes
Microscopy
Microscopy, Atomic Force
Molecular Dynamics Simulation
Molecular Sequence Data
Nanotechnology - methods
P branes
Peptides
Phospholipids
Phospholipids - chemistry
Phospholipids - metabolism
Physical Sciences
Pores
Protein Engineering
Proteins
Research facilities
Scientific imaging
Spectrometry, Mass, Secondary Ion
nanoscopy
de novo protein design
antibiotics
innate host defense
nanometrology
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Summary:Antimicrobial peptides are postulated to disrupt microbial phospholipid membranes. The prevailing molecular model is based on the formation of stable or transient pores although the direct observation of the fundamental processes is lacking. By combining rational peptide design with topographical (atomic force microscopy) and chemical (nanoscale secondary ion mass spectrometry) imaging on the same samples, we show that pores formed by antimicrobial peptides in supported lipid bilayers are not necessarily limited to a particular diameter, nor they are transient, but can expand laterally at the nano-to-micrometer scale to the point of complete membrane disintegration. The results offer a mechanistic basis for membrane poration as a generic physicochemical process of cooperative and continuous peptide recruitment in the available phospholipid matrix.
Bibliography:http://dx.doi.org/10.1073/pnas.1222824110
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Edited by Hiroshi Nikaido, University of California, Berkeley, CA, and approved April 16, 2013 (received for review January 2, 2013)
1P.D.R., H.J., and S.R. contributed equally to this work.
Author contributions: B.W.H., A.W., J.C., C.R.M.G., and M.G.R. designed research; P.D.R., H.J., S.R., A.P., B.L., M.C., P.J.J., J.R., U.I.M.G., and G.J.M. performed research; U.I.M.G. and B.K. contributed new reagents/analytic tools; P.D.R., H.J., S.R., A.P., B.L., M.C., P.J.J., J.R., B.K., G.J.M., B.W.H., A.W., J.C., C.R.M.G., and M.G.R. analyzed data; and M.G.R. wrote the paper.
ISSN:0027-8424
1091-6490
1091-6490
DOI:10.1073/pnas.1222824110